Brain Chemistry and Altitude in Bipolar Disorder

双相情感障碍的脑化学和海拔

• 批准号: 8680018
• 负责人: PERRY FRANKLIN RENSHAW
• 金额: --
• 依托单位: VA SALT LAKE CITY HEALTHCARE SYSTEM
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-07-01 至 2017-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8680018
• 关键词: Acidosis; Address; Adult; Advocate; Affect; Affective; Alkalosis; Altitude; Anterior; Biological; Biological Markers; Bipolar Depression; Bipolar Disorder; Blood gas; Brain; Brain Chemistry; Brain scan; Caring; Cerebrum; Cities; Clinical; Clinical assessments; Cross-Sectional Studies; DSM-V; Data; Depressed mood; Depression and Suicide; Diagnosis; Diagnostic; Diagnostic Procedure; Disabled Persons; Discipline; Disease; Education; Effectiveness; Endogenous Factors; Energy Metabolism; Enrollment; Environmental Risk Factor; Functional disorder; Glutamates; Glutamine; Goals; Health Care Costs; Homeostasis; Human; Hyperventilation; Hypoxia; Impaired cognition; Incidence; Individual; Lead; Link; Lithium; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Major Depressive Disorder; Manic; Measurement; Measures; Medical; Mental Depression; Mental disorders; Mission; Moods; National Institute of Mental Health; Neurobiology; Occipital lobe; Oxygen; Oxygen Consumption; Partial Pressure; Patients; Phosphorus; Population; Protons; Publications; Publishing; Relative (related person); Reporting; Research; Research Design; Risk Factors; Schizophrenia; Scientist; Sea; Site; Sodium Chloride; Strategic Planning; Suicide; Symptoms; Syndrome; System; Therapeutic; Unemployment; United States Department of Veterans Affairs; Veterans; World Health Organization; base; cingulate cortex; depressive symptoms; disability; foot; frontal lobe; improved; in vivo; insight; male; meter; mitochondrial dysfunction; neuroimaging; novel; novel diagnostics; programs; public health relevance; reducing suicide; research study; suicide rate; trait; treatment response; treatment strategy; volunteer

DESCRIPTION (provided by applicant): Bipolar disorder is a prevalent and severe psychiatric disorder marked by alternating episodes of depression and mania. In the Department of Veterans Affairs (VA), nearly 80,000 Veterans received care for bipolar disorder in 2004, a 40% increase from 1999. Bipolar disorder imposes a substantial medical burden on Veterans, and is associated with the highest health care costs of any psychiatric disorder in the VA system. Moreover, in male Veterans bipolar disorder is a significant risk factor for suicide. The World Health Organization ranks bipolar disorder as the sixth leading cause of global medical disability. Despite decades of research, the illness remains poorly understood, and no new treatment has surpassed lithium's effectiveness for the majority of patients. There is a critical need for research studies aimed at understanding the neurobiology of bipolar disorder, to improve our diagnostic and treatment strategies. Brain pH is closely linked to affective functioning, and is influenced by a range of internal and external factors. One such environmental factor may be altitude. Extreme altitudes are associated with a decreased partial pressure of inspired oxygen, and this hypobaric hypoxia results in significant cognitive impairment. However, the effect of moderate changes in altitude on brain chemistry is not well understood. Recent publications show that within the U.S., altitude is associated with an increased rate of suicide that begins at the modest altitude of ~2,000 feet, an effect that may be strongest in bipolar disorder. In terms of endogenous factors, it is hypothesized that decreased brain pH in bipolar disorder may represent a biologic trait of the illness. Decreased brain pH has been linked to altered brain lactate and glutamate levels in bipolar disorder. Research is needed to clarify the relationship between mood, brain chemistry and altitude in bipolar disorder. To address this need, we propose to use magnetic resonance spectroscopy (MRS) neuroimaging together with clinical assessments, to study the relationship between brain pH, glutamate, lactate and altitude in Veterans with bipolar disorder. The proposal features a novel cross-sectional study design, in which brain scans will be performed on subjects with bipolar disorder at two altitudes: Salt Lake City, UT (4,700 feet) and Belmont, MA (44 feet). A total of 120 subjects will be enrolled, including 40 depressed bipolar subjects (20 per site), 40 euthymic bipolar subjects (20 per site), and 40 healthy controls (20 per site). All subjects will undergo MRS brain scans to measure their brain pH, glutamate and lactate levels. The proposed study will provide insight into the interrelationship of brain chemistry, mood state and altitude in bipoar disorder. The results of the study may help scientists develop new diagnostic methods, or new treatment approaches for Veterans with bipolar disorder.

描述（由申请人提供）： 双相情感障碍是一种普遍且严重的精神疾病，其特征是抑郁和躁狂交替发作。在退伍军人事务部 (VA)，2004 年有近 80,000 名退伍军人接受双相情感障碍治疗，比 1999 年增加了 40%。双相情感障碍给退伍军人带来了沉重的医疗负担，并且与所有精神科疾病中最高的医疗保健费用相关VA 系统紊乱。此外，对于男性退伍军人来说，双相情感障碍是自杀的一个重要危险因素。 世界卫生组织将双相情感障碍列为全球医疗残疾的第六大原因。尽管经过了数十年的研究，人们对这种疾病的了解仍然知之甚少，而且对于大多数患者来说，没有任何新的治疗方法能够超越锂的有效性。迫切需要旨在了解双相情感障碍的神经生物学的研究，以改进我们的诊断和治疗策略。 大脑 pH 值与情感功能密切相关，并受到一系列内部和外部因素的影响。其中一种环境因素可能是海拔高度。极端海拔与吸入氧分压降低有关，这种低压缺氧会导致严重的认知障碍。然而，海拔适度变化对大脑化学物质的影响尚不清楚。最近的出版物显示，在美国，海拔高度与自杀率增加有关，自杀率从大约 2,000 英尺的中等海拔开始，这种影响在双相情感障碍中可能最强。就内源性因素而言，双相情感障碍患者大脑 pH 值降低可能代表该疾病的生物学特征。双相情感障碍患者大脑 pH 值降低与大脑乳酸和谷氨酸水平改变有关。需要进行研究来阐明双相情感障碍的情绪、大脑化学物质和海拔之间的关系。 为了满足这一需求，我们建议将磁共振波谱 (MRS) 神经影像与临床评估结合使用，研究患有双相情感障碍的退伍军人的大脑 pH 值、谷氨酸、乳酸和海拔之间的关系。该提案采用了一种新颖的横断面研究设计，其中将对双相情感障碍患者在两个海拔高度进行脑部扫描：犹他州盐湖城（4,700 英尺）和马萨诸塞州贝尔蒙特（44 英尺）。总共将招募 120 名受试者，包括 40 名抑郁双相受试者（每个中心 20 名）、40 名情绪正常双相受试者（每个中心 20 名）和 40 名健康对照者（每个中心 20 名）。所有受试者都将接受 MRS 脑部扫描，以测量他们的大脑 pH 值、谷氨酸和乳酸水平。 拟议的研究将深入了解双相障碍中大脑化学物质、情绪状态和海拔的相互关系。该研究的结果可能有助于科学家为患有双相情感障碍的退伍军人开发新的诊断方法或新的治疗方法。